The specific aims of this research are the genetic and molecular characterization of a candidate gene for disorders in growth, neurological function, behavior and fertility associated with three independent radiation induced deletions at the p locus. These three mutations, p6H, p25H and pb5 are associated with deletions that disrupt the p gene and an adjacent gene involved in the disorders listed above. It is possible that a common neuro-endocrine defect could explain the diverse phenotypes seen in these mutant mice. The region of mouse chromosome 7 where these deletions lie is syntenic with human chromosome l5ql1-13. This region of human chromosome 15 has been associated with Prader-Willi and Angelman syndromes. Cloned fragments from the region deleted in the mentioned mutants show similarity to human homologous cDNA sequences and RCC1 repeats. The candidate gene encodes a large (about l5kb) transcript and several cDNA clones have been isolated and partially sequenced. The complete cDNA will be isolated and its entire sequence will be determined. Spatial expression of this gene will be determined using ill situ hybridization. A testable model describing the role this gene product might play in growth, neurological processes, behavior and fertility is proposed, derived from predictions based on the cDNA sequence and the spatial and temporal expression of this gene. This model will be refined as more data are accumulated and will then be tested to further delineate this role of this gene product in the processes listed.